Residual alkylating agent detector and method therefor

ABSTRACT

A FRANGIBLE AMPULE CONSTRUCTED OF MATERIAL WHICH IS IMPERMEABLE TO ALKYLATING AGENT, AND CONTAINING AN INDICATOR, THE DEVICE IS SUITABLE FOR MONITORING RESIDUAL ALKYLATING AGENT INSIDE A STERILE, SEALED PACKAGE.

SH-USlNG CHENG June 12, 1973 RESIDUAL ALKYLATING AGENT DETECTOR AND METHOD THEREFOR Filed July 1, 1971 INVENTOR.

SHU-SING CHENG ATTORNEY United States Patent 3,738,811 RESIDUAL ALKYLATING AGENT DETECTOR AND METHOD THEREFOR Shu-Sing Cheug, Carpentersville, Ill., assignor to The Kendall Company, Boston, Mass. Filed July 1, 1971, Ser. No. 158,764 Int. Cl. B6511 79/00; G01n 31/22, 33/16 U.S. Cl. 23232 R 26 Claims ABSTRACT OF THE DISCLOSURE A frangible ampule constructed of material which is impermeable to alkylating agent, and containing an indicator; the device is suitable for monitoring residual alkylating agent inside a sterile, sealed package.

This invention relates to a device for monitoring the absence of alkylating agent in an environment and to a method therefor. More particularly, this invention relates to a device and method for insuring that packages previously sterilized by means of an alkylating agent are free from said alkylating agent prior to use.

In the sterilization of hospital supplies, such as surgical instruments, dressings, gloves, plastic syringes and various other medical devices, there is a growing trend toward the use of alkylating agents as the sterilization agent. The most popular sterilizing alkylating agent presently employed is ethylene oxide gas, generally in admixture with an inert gaseous diluent, such as carbon dioxide, nitrogen, trichloromonofluorornethane, dichlorodifluoromethane, and the like. Since ethylene oxide gas readily diffuses through all of the commonly employed packaging materials and is highly effective in killing microorganisms at temperatures well below those required for heat sterilization techniques, it enables efiici'ent sterilization of many items, particularly those made of thermoplastic materials, which cannot withstand heat sterilization.

While the use of ethylene oxide as a sterilization agent has achieved widespread acceptance, the undesirability of using sterilized articles contaminated with the sterilization agent is a recognized problem. From a toxicological viewpoint, it is imperative that the sterilized article be free from even traces of alkylating agent prior to use. While such a condition may be achieved by storing the package for an appropriate length of time to insure dissipation of the alkylating agent, the economic drawbacks to such a procedure will be apparent.

Now it has been found that the device of this invention can be employed to indicate the absence of alkylating agent in an environment, thus insuring the safe use of the sterilized articles contained therein.

This device basically comprises a frangible ampule constructed of material which is impermeable to alkylating agents, and containing an indicator capable of visibly exhibiting a color development or change upon being exposed to an alkylating agent.

The device of this invention will be better understood by reference to the following description of the invention and the accompanying drawings in which:

FIG. 1 is a side view of one embodiment of a device of this invention; and

FIG. 2 is a top plan view of a package containing a plurality of devices constructed according to another embodiment of the invention.

Referring to FIG. 1, there is shown a device 10 comprising a glass ampule 12, and sealed within the container an indicator 14.

The frangible ampule 12 must be impermeable to the particular alkylating agent employed in the sterilization process, since exposure to the immediate environment must occur only when the ampule is ruptured. Thus, glass or plastic having the appropriate physical and chemical properties, can be suitably employed in the construction of the ampule. While the transparency of the material is not a factor, since a liquid indicator having the ability to seep out of the container and thus become visible can be used, it is convenient to employ a substantially transparent material so that the presence or absence of color change upon exposure to the immediate environment will be readily apparent.

While frangible ampule 12 is shown as being cylindrical, any shape can be employed provided the ampule is hermetically sealed. The indicator can be inserted into the ampule under conditions which render the inner surface of the ampule sterile, or only the outer surface thereof can be sterilized, either at the time of manufacture or when sterilizing a package containing the ampule as described hereinafter.

In an alternate embodiment of the invention, the ampule may be constructed so as to be frangible in a predetermined part thereof upon the application of pressure, thus facilitating the rupturing of the ampule according to the method described hereinafter. This can be achieved by various methods, such as scoring or forming the ampule with a reduced wall thickness in the area where breakage is desired.

Indicator 14 can be any substance or system, in any physical form, which exhibits a visible color development or change in the presence of ethylene oxide. The term indicator includes, but is not limited to, solids, liquids, and inks containing one or more dissolved indicating compounds. While pH indicators such as disclosed in U.S. Pats. 2,998,306; 3,098,715 and 3,258,312 can be used, preferred embodiments of this invention utilize the substituted pyridines, quinolines and isoquinolines disclosed in my copending application Ser. No. 32,460 filed Apr. 27, 1970, now Pat. No. 3,627,469, and the entire disclosure thereof is herewith incorporated by reference. Thus, an indicator selected from the following group is preferably employed:

and salts thereof, wherein at least one and not more than two of the R and R groups are hydrogen; R and R are independently selected from the group consisting of hydrogen,

\N 1 or 2 onon-onon-W and 2 ll -CRs R is hydrogen, halogen or alkyl; X is hydrogen, N=O, NO OH, SH, --CH=N-OH, alkyl or halogen, Y is hydrogen, N=O, OH, SH, CH=NOH, alkyl or halogen; Z is oxygen or sulfur; R is OH, NH NHNH or alkoxyl; at least one of the R groups is OH, SH or --CH=NOH, and the other R groups are hydrogen.

FIG. 2 depicts a package 20 comprising polyethylene plastic envelope 22 and having sealed therein a sterile article diagrammatically represented at 24. The package also contains a card 26 having mounted thereon four glass ampules 12, each having an ink containing dissolved indicating compound absorbed or adsorbed on a piece of thread 28 which functions as a carrier. Glass ampules 12 are contained within polyethylene receptacles 30, these receptacles being permeable to the alkylating agent and being secured to card 26 by elastic thread 32.

While the use of a carrier is optional, it provides for a neater unit where an ink or liquid indicator is used, since spillage of compound upon breaking the glass ampules is obviated. Furthermore, the use of a carrier renders the system more sensitive to detection of the alkylating agent, since it is not necessary for the alkylating agent to dissolve in a liquid medium. It will be apparent that other carriers such as gauze, cloth, paper etc. can be employed.

Although receptacles 30 are illustrated as being made of polyethylene, they can be constructed of any flexible, substantially transparent material. Preferably they comprise an appropriate plastic, which serves the triple function of trapping residual alkylating agent in the area immediately surrounding the ampule containing the indicator, preventing spillage or leakage when the ampule is broken, and maintaining complete sterility within the package where the inside surface of the ampule is not sterile. Alternately, receptacles 30 can comprise strips of transparent material sealed around the periphery of the ampules by conventional means, such as adhesives, etc. If desired, the same function can be achieved by vacuum blister packaging frangible ampules 12 on card 26 using a single sheet of plastic, or employing a polyethylene coated glass for the ampules.

While FIG. 2 depicts a card having four frangible ampules mounted thereon, the number of such ampules in a given package is not critical to the invention. Thus, a single ampule can be provided where only one check is contemplated, multiple ampules being employed for sequential testing as described hereinafter. Where more than one ampule is provided, it is desirable to mount the frangible ampules on a card as shown in FIG. 2, to simplify use and eventual disposal. If desired, the frangible ampules can be designated by differential numerals or letters on the ca d to id the q tial testi g e hod.

It is an optional feature of this invention that, if the article to be sterilized is constructed of a suitable plastic, the same material can be used for receptacle 30. This selection procedure insures that there is no residual ethylene oxide in the sterilized article itself, in addition to indicating an absence of the same in the container.

Although container 22 as shown in FIG. 2 is a polyethylene bag, any conventional packaging material for sterilized articles can be used, the only requirement being that the selected material is permeable to alkylating agent and impermeable to bacteria, so that the sterile condition of the article contained therein can be maintained throughout.

Prior to practicing the method of this invention, a package is provided with one or more frangible ampules containing an appropriate indicator. The package is then subjected to sterilization by means of an alkylating agent. This procedure sterilizes both the article or articles in the package and the outer surface of the frangible ampule. Attainment of a sterilized condition can be insured by means of an indicator, e.g., one similar or identical to that included in the device, but without an impermeable shield.

When it is desired to use the sterilized article, according to the method of this invention one exposes the environment within the sealed, sterile package to an indicator capable of visibly exhibiting a color development or change upon being subjected to an alkylating agent, and observes the presence or absence of color development or change in the indicator. This can be done by applying pressure to the frangible ampule through the package and the flexible transparent receptacle, if any. In the absence of a visual color development or change, the sterilized article is ready for use. If a color development or change does occur, and additional devices are present in the package, the step is repeated at dilferent times until no color development or change is observed. It will be readily appreciated that the method of this invention is non-destructive in that only the ampule, and not the container is ruptured, thus maintaining the sterilized condition within the package.

Although this invention has been described with particular reference to ethylene oxide sterilization procedures, other alkylating agents such as propylene oxide, B-propiolactone, ethyleneimines, alkyl sulfates, alkyl halides, nitrogen mustards, aziridines, sulfonic esters, and various epoxides can be used.

While this invention has been described above in detail with respect to certain preferred embodiments of the invention as illustrated in the drawings, other modifications and design changes are also contemplated which are within the spirit and scope of the appended claims.

What is claimed is:

1. A device for monitoring the absence of an alkylating agent in an environment which comprises a frangible ampule containing an indicator capable of visibly exhibiting a color development or change upon being subjected to said alkylating agent, said ampule having a sterile outer surface and being impermeable to said alkylating agent.

2. The device of claim 1 wherein said frangible ampule is substantially transparent.

3. The device of claim 1 wherein a carrier for said indicator is disposed within said frangible ampule.

4. A device for monitoring the absence of an alkylating agent in an environment which comprises an ampule containing an indicator capable of visibly exhibiting a color development or change upon being subjected to said alkylating agent, said ampule being frangible in a predetermined part thereof upon the application of pressure, and being impermeable to said alkylating agent.

5. The device of claim 4 wherein said ampule is scored in the predetermined part.

6. The device of claim 4 wherein said ampule is formed with a reduced wall thickness in the predetermined part,

7. The device of claim 4 wherein said indicator is selected from the group consisting of and salts thereof, wherein at least one and not more than two of the R and R groups are hydrogen; R and R are independently selected from the group consisting 1 of hydrogen,

CHz-OH, CHr-CHg-OH, CHz-CHg-SOaH, -CH=CH2,

and

R is hydrogen, halogen or alkyl; X is hydrogen, --N=O, -NO OH, 4H, CH=N-H, alkyl or halogen, Y is hydrogen, N=O, OH, SH, --CH=NOH, alkyl or halogen; Z is oxygen or sulfur; R is OH, -NH -NHNH or alkoxyl; at least one of the R groups is OH, --SH or CH=NOH, and the other R groups are hydrogen.

8. A device for monitoring the absence of an alkylating agent in an environment which comprises a frangible ampule containing a carrier having absorbed or adsorbed thereon an indicator capable of visibly exhibiting a color development or change upon being subjected to said alkylating agent, said ampule having a sterile inner surface.

9. The device of claim 1 further comprising a flexible,

substantially transparent receptacle for said frangible ampule, said receptacle being permeable to said alkylating agent.

10. The device of claim 4 wherein said frangible ampule is glass, said flexible, substantially transparent receptacle is plastic and said alkylating agent is ethylene oxide.

11. A device for monitoring the absence of an alkylating agent in an environment which comprises a frangible ampule containing an indicator capable of visibly exhibiting a color development or change upon being subjected to said alkylating agent, said ampule being impremeable to alkylating agent, said ampule being sealed in a flexible, substantially transparent receptacle which is permeable to said alkylating agent.

12. A device for monitoring the absence of an alkylating agent in an environment which comprises a frangible ampule containing an indicator capable of visibly exhibiting a color development or change upon being subjected to said alkylating agent, said ampule being frangible in a predetermined part thereof upon the application of pressure, and being impermeable to said alkylating agent, said ampule being sealed in a flexible, substantially transparent receptacle which is permeable to said alkylating agent.

13. A package comprising a container permeable to an alkylating agent and sealed within said container at least one sterile article and at least one device as claimed in claim 1.

14. A package comprising a container permeable to an alkylating agent and sealed within said container at least one sterile article and at least one device as claimed in claim 4.

15. The package of claim 14 wherein said container is comprised of a flexible, substantially transparent plastic.

16. A package comprising a container permeable to an 5 alkylating agent and sealed within said container a device as claimed in claim 8.

17. A package comprising a container permeable to an alkylating agent and sealed within said container a device as claimed in claim 9.

18. A package comprising a container permeable to an alkylating agent and sealed within said container 2. device as claimed in claim 11.

19. A package comprising a container permeable to an alkylating agent and sealed within said container a device as claimed in claim 12.

20. A method for non-destructively testing for the presence of residual alkylating agent inside a sealed, sterile package which comprises (a) exposing the environment within a sealed, sterile package which has been previously sterilized by means of an alkylating agent to an indicator capable of visibly exhibiting a color development or change upon being subjected to said agent, and

(b) observing the presence or absence of color development or change in said indicator.

21. The method of claim 20 wherein said alkylating agent is ethylene oxide.

22. A method for non-destructively testing for the presence of residual alkylating agent inside a package as claimed in claim 13 which has been sterilized by means of an alkylating agent which comprises rupturing the frangible ampule of at least one of said devices without breaking said container, and observing the presence or absence of color development or change upon exposure of the indicator to the environment within said container.

23. A method for non-destructively testing for the presence of residual alkylating agent inside a package as claimed in claim 14 which has been sterilized by means of an alkylating agent which comprises rupturing the frangible ampule of at least one of said devices without breaking said container, and observing the presence or absence of color development or change upon exposure of the indicator to the environment within said container.

24. A method for non-destructively testing for the presence of residual alkylating agent inside a package as claimed in claim 18 which has been sterilized by means of an alkylating agent which comprises rupturing the frangible ampule of at least one of said devices without breaking said container, and observing the presence or absence of color development or change upon exposure of the indicator to the environment within said container.

25. A method for non-destructively testing for the presence of residual alkylating agent inside a package as claimed in claim 19 which has been sterilized by means of an alkylating agent which comprises rupturing the frangible ampule of at least one of said devices without breaking said container, and observing the presence or absence of color development or change upon exposure of the indicator to the environment within said container.

26. A non-destructive method of indicating the absence of alkylating agent in a package which has been subjected to sterilization by means of an alkylating agent and which has sealed therein a plurality of devices as claimed in claim 1 which comprises sequentially rupturing the frangible ampules of said devices until the absence of color the environment Within said package is observed.

References Cited UNITED STATES PATENTS Shepherd 23-232 R Huyck et a1 23--232 R X Grosskopf 23-232 R X Huyck et a1 H6-l 14 AM 8 7 3,620,679 11/ 1971 DeVaughn 23-259 3,627,469 12/1971 Cheng 23---232 R JOSEPH SCOVRONEK, Primary Examiner 5 R. M. REESE, Assistant Examiner US. Cl. X.R.

23-230 R, 253 R, 254 R; 206-47 R, 63.2 R 

